title: Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats.
abstract: Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent.
authors.affiliation: Center for Translational Biomedical Research and Dept. of Nutrition, Univ. of North Carolina at Greensboro, North Carolina Research Campus, 500 Laureate Way, Suite 4226, Kannapolis, NC 28081. z_zhou@uncg.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Sun
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Tan
authors.forename: Xinguo
authors.initials: X
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Zhanxiang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000145:classification / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D025461:Feedback, Physiological; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D014280:Triglycerides; D000431:Ethanol; C052387:cocoa butter
keywords: alcohol; endotoxemia; inflammation; liver injury; saturated fat